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Hyaluronan hydrogel: an appropriate three-dimensional model for evaluation of anticancer drug sensitivity.

机译:透明质酸水凝胶:评估抗癌药物敏感性的适当三维模型。

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摘要

The extracellular polysaccharide hyaluronan (HA) controls cell migration, differentiation and proliferation, and contributes to the invasiveness of human cancers. In order to investigate the sensitivity of cancer cells to antimitotic agents, we developed a cross-linked HA hydrogel, a three-dimensional matrix in which cells can invade and grow. We have studied three cell lines (SA87, NCI-H460 and H460M), from primary tumors and metastases, that migrated into the HA hydrogel and proliferated giving rise to clusters and colonies. Concurrently, we studied the growth of these cell lines in a usual monolayer culture system. In these two models, increasing concentrations of doxorubicin and 5-fluorouracil were evaluated for their ability to inhibit tumor cell growth and colony formation. Taken together, our data suggest that the cancer cells were more resistant in the three-dimensional model than in monolayer cell systems. The antimitotic drugs were efficient after 24h of treatment in the monolayer cultures, whereas they were significantly efficient only after one week of incubation in the HA hydrogels. Herein, we show that this cross-linked matrix provides a three-dimensional model particularly appropriate for investigating mechanisms involved in cancer cell line sensitivity to antimitotic drugs.
机译:细胞外多糖透明质酸(HA)控制细胞迁移,分化和增殖,并有助于人类癌症的侵袭性。为了研究癌细胞对抗有丝分裂剂的敏感性,我们开发了一种交联的HA水凝胶,这是一种三维矩阵,细胞可以在其中侵入并生长。我们已经研究了来自原发性肿瘤和转移灶的三种细胞系(SA87,NCI-H460和H460M),这些细胞系迁移到HA水凝胶中并增殖,形成簇和集落。同时,我们研究了在通常的单层培养系统中这些细胞系的生长。在这两个模型中,评估了浓度增加的阿霉素和5-氟尿嘧啶抑制肿瘤细胞生长和集落形成的能力。综上所述,我们的数据表明,在三维模型中,癌细胞比在单层细胞系统中更具抵抗力。在单层培养物中处理24小时后,抗​​有丝分裂药物有效,而仅在HA水凝胶中温育一周后,它们才显着有效。在这里,我们表明,这种交联的基质提供了一个三维模型,特别适合于研究癌细胞系对有丝分裂药物的敏感性所涉及的机制。

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